Differential expression of terminal transferase (TdT) in acute lymphocytic leukaemia expressing myeloid antigens and TdT positive acute myeloid leukaemia as compared to myeloid antigen negative acute lymphocytic leukaemia

Elisabeth M. Paietta, Janis Racevskis, J. M. Bennett, P. H. Wiernik

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

We examined whether the allegedly aberrant expression of the lymphoid lineage associated DNA polymerase, terminal deoxynucleotidyl transferase (TdT), in acute myeloid leukaemia (AML) is associated with alterations of the enzyme at the cellular, biochemical or transcriptional level when compared to lymphoid leukaemia (ALL), either lacking or expressing myeloid antigens. By flowcytometric analysis, the intensity of TdT staining with monoclonal anti-TdT antibody was considerably weaker in TdT+AML and myeloid+ ALL (M+ALL) than in myeloid- ALL (M-ALL). TdT enzyme activity in TdT+AML was on an average 10%, and in M+ALL 25% of that measured in M-ALL. Anti-TdT antibodies precipitated a major specific protein of identical relative molecular mass (58 kD) from metabolically labelled TdT+ myeloblasts and lymphoblasts. By Northern blot analysis and ribonuclease protection assay, TdT transcript levels were significantly lower in TdT+ myeloblasts and M+ lymphoblasts than in M-ALL (P < 0.0001). The level of TdT transcription in AML was independent of the simultaneous expression of lymphoid-specific antigens, such as CD2 and CD19. Our data demonstrate that TdT expression is downregulated in association with myeloid features, not only in AML but also in ALL. This observation may provide the molecular basis for the differential therapeutic responsiveness, particularly to glucocorticoids, in these various leukaemia subtypes.

Original languageEnglish (US)
Pages (from-to)416-422
Number of pages7
JournalBritish Journal of Haematology
Volume84
Issue number3
StatePublished - 1993

Fingerprint

DNA Nucleotidylexotransferase
Transferases
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute Myeloid Leukemia
Antigens
Granulocyte Precursor Cells
Lymphoid Leukemia
Antibodies
DNA-Directed DNA Polymerase
Enzymes
Ribonucleases
Northern Blotting
Glucocorticoids
Leukemia
Down-Regulation

ASJC Scopus subject areas

  • Hematology

Cite this

@article{a9f7f264777b4d93bd5f4d7148f0fa8b,
title = "Differential expression of terminal transferase (TdT) in acute lymphocytic leukaemia expressing myeloid antigens and TdT positive acute myeloid leukaemia as compared to myeloid antigen negative acute lymphocytic leukaemia",
abstract = "We examined whether the allegedly aberrant expression of the lymphoid lineage associated DNA polymerase, terminal deoxynucleotidyl transferase (TdT), in acute myeloid leukaemia (AML) is associated with alterations of the enzyme at the cellular, biochemical or transcriptional level when compared to lymphoid leukaemia (ALL), either lacking or expressing myeloid antigens. By flowcytometric analysis, the intensity of TdT staining with monoclonal anti-TdT antibody was considerably weaker in TdT+AML and myeloid+ ALL (M+ALL) than in myeloid- ALL (M-ALL). TdT enzyme activity in TdT+AML was on an average 10{\%}, and in M+ALL 25{\%} of that measured in M-ALL. Anti-TdT antibodies precipitated a major specific protein of identical relative molecular mass (58 kD) from metabolically labelled TdT+ myeloblasts and lymphoblasts. By Northern blot analysis and ribonuclease protection assay, TdT transcript levels were significantly lower in TdT+ myeloblasts and M+ lymphoblasts than in M-ALL (P < 0.0001). The level of TdT transcription in AML was independent of the simultaneous expression of lymphoid-specific antigens, such as CD2 and CD19. Our data demonstrate that TdT expression is downregulated in association with myeloid features, not only in AML but also in ALL. This observation may provide the molecular basis for the differential therapeutic responsiveness, particularly to glucocorticoids, in these various leukaemia subtypes.",
author = "Paietta, {Elisabeth M.} and Janis Racevskis and Bennett, {J. M.} and Wiernik, {P. H.}",
year = "1993",
language = "English (US)",
volume = "84",
pages = "416--422",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Differential expression of terminal transferase (TdT) in acute lymphocytic leukaemia expressing myeloid antigens and TdT positive acute myeloid leukaemia as compared to myeloid antigen negative acute lymphocytic leukaemia

AU - Paietta, Elisabeth M.

AU - Racevskis, Janis

AU - Bennett, J. M.

AU - Wiernik, P. H.

PY - 1993

Y1 - 1993

N2 - We examined whether the allegedly aberrant expression of the lymphoid lineage associated DNA polymerase, terminal deoxynucleotidyl transferase (TdT), in acute myeloid leukaemia (AML) is associated with alterations of the enzyme at the cellular, biochemical or transcriptional level when compared to lymphoid leukaemia (ALL), either lacking or expressing myeloid antigens. By flowcytometric analysis, the intensity of TdT staining with monoclonal anti-TdT antibody was considerably weaker in TdT+AML and myeloid+ ALL (M+ALL) than in myeloid- ALL (M-ALL). TdT enzyme activity in TdT+AML was on an average 10%, and in M+ALL 25% of that measured in M-ALL. Anti-TdT antibodies precipitated a major specific protein of identical relative molecular mass (58 kD) from metabolically labelled TdT+ myeloblasts and lymphoblasts. By Northern blot analysis and ribonuclease protection assay, TdT transcript levels were significantly lower in TdT+ myeloblasts and M+ lymphoblasts than in M-ALL (P < 0.0001). The level of TdT transcription in AML was independent of the simultaneous expression of lymphoid-specific antigens, such as CD2 and CD19. Our data demonstrate that TdT expression is downregulated in association with myeloid features, not only in AML but also in ALL. This observation may provide the molecular basis for the differential therapeutic responsiveness, particularly to glucocorticoids, in these various leukaemia subtypes.

AB - We examined whether the allegedly aberrant expression of the lymphoid lineage associated DNA polymerase, terminal deoxynucleotidyl transferase (TdT), in acute myeloid leukaemia (AML) is associated with alterations of the enzyme at the cellular, biochemical or transcriptional level when compared to lymphoid leukaemia (ALL), either lacking or expressing myeloid antigens. By flowcytometric analysis, the intensity of TdT staining with monoclonal anti-TdT antibody was considerably weaker in TdT+AML and myeloid+ ALL (M+ALL) than in myeloid- ALL (M-ALL). TdT enzyme activity in TdT+AML was on an average 10%, and in M+ALL 25% of that measured in M-ALL. Anti-TdT antibodies precipitated a major specific protein of identical relative molecular mass (58 kD) from metabolically labelled TdT+ myeloblasts and lymphoblasts. By Northern blot analysis and ribonuclease protection assay, TdT transcript levels were significantly lower in TdT+ myeloblasts and M+ lymphoblasts than in M-ALL (P < 0.0001). The level of TdT transcription in AML was independent of the simultaneous expression of lymphoid-specific antigens, such as CD2 and CD19. Our data demonstrate that TdT expression is downregulated in association with myeloid features, not only in AML but also in ALL. This observation may provide the molecular basis for the differential therapeutic responsiveness, particularly to glucocorticoids, in these various leukaemia subtypes.

UR - http://www.scopus.com/inward/record.url?scp=0027200636&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027200636&partnerID=8YFLogxK

M3 - Article

VL - 84

SP - 416

EP - 422

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 3

ER -